1.1. Field of the Invention
The present invention relates to biomedical materials comprising an extract from Chondrichthyes. More specifically, the present invention relates to biomedical materials using Chondrichthyes-derived collagen which are applicable as various implant materials such as a wound cover, artificial skin, artificial bone, artificial cartilage and artificial tendon, as well as methods for preparing such biomedical materials.
1.2. Description of the Prior Art
When a bone defect has complicated due to some lesion such as an injury, osteoncus or inherent disease, the filling of the defect may be therapeutically necessary. Also, when skin has been damaged by some injury such as a burn, especially when a part of the skin has been lost in full-thickness or almost full-thickness, filling may be necessary.
Conventionally, when filling a bone defect, an autologous bone graft taken from other part of the patient body such as the illium or the fibula has been used if the defect is not so big. When filling a big bone defect in the skeletal system, an artificial bone has been prepared using a ceramic of metals such as titanium, alumina and zirconia or oxides thereof, a ceramic such as apatite and a composite material of these substances to thereby supplement the defect.
When filling a skin defect, a non-bioabsorbable or bioabsorbable, sheet-type wound cover or artificial skin has been used. The term "wound cover" used herein means a material which merely covers the site of skin defect physically, and the term "artificial skin" used herein means a substitute skin which has the possibility of taking the place of skin grafting.
As a non-bioabsorbable thin sheet-type wound cover, a thin, elastic, synthetic polymer sheet made from polyurethane, silicone or the like may be given. As an bioabsorbable wound cover, freeze-dried porcine corium, a sheet made of chitin, collagen, alginic acid and the like are known. In addition to these sheet-type wound covers, powder of a cellulose derivative is also known which is applied to the injured site to form a sheet thereon. As artificial skin, one composed of cell-free materials and a cultured skin which is obtained by two-dimensionally culturing human epidermal cells are known. As a material for the former artificial skin, spongy collagen is known.
Those materials used for the above-mentioned purposes are required, from the viewpoint of organisms, to manifest positive functions and yet to fit compatibly with organisms (i.e., to have biocompatibility). Biocompatibility can be roughly divided into histocompatibility and blood compatibility. When a material of low biocompatibility is embedded in or contacted with an organism, components eluted from the material or worn out pieces of the material separated from its surface penetrate into the tissue surrounding the material or spread in the organism through blood circulation to cause a systemic tissue reaction, which results in various problems such as necrosis of a tissue. On the other hand, from the viewpoint of material itself, the above-mentioned materials are required not to deteriorate upon contact with organisms and to maintain for a specific period of time physical and chemical properties that could satisfy a required function.
Further, these materials should not differ greatly in mechanical properties from the tissues of organisms to which they are to be jointed. In other words, these materials need to have mechanical biocompatibility. This is to prevent the occurrence of incompatible distortion or stress concentration on or near the junction which may cause breakage or abnormality at the junction and thus make it impossible for the jointed material to manifest the function of interest.
These materials are further required to be capable of perfect sterilization and disinfection and to be capable of standing these treatments.
However, conventional materials described above have been pointed out to have several problems. For example, since metals are extremely high in strength, they are indispensable as a substitute skeleton which effects biofunctions. However, when a metal is used in filling a bone defect, an organism does not recognize the metal as a part of the self and, thus, a problem will occur in a long-term use. Even if the metal has been coated with a ceramic which is well biocompatible with the organism, there is a drawback that the ceramic will be shed from the metal during the course of use. Thus, this technique has not been put to practical use.
Collagen is mainly used in wound covers and artificial skin and such collagen is derived from bovine. It is known that bovine-derived collagen has antigenicity. Thus, it is necessary to carry out a special treatment or use fetal collagen without antigenicity.
There are blood groups in human blood and major histocompatibility antigens in human tissues. It is well known that a transfusion of blood not matching the blood group of a patient induces rejection that may eventually kill the patient. As such blood groups, the ABO system, the Rh system, the Ii system, the P system, the MN system and other blood groups are known. Accordingly, when a blood transfusion, bone marrow transplantation, organ transplantation from a living donor, or tissue transplantation from a living donor is to be performed, selection of a donor compatible with the patient in blood group is very critical for making the transfusion or transplantation. successful, though it is difficult to find out a completely matching donner for individual patients.
Such a problem is also encountered similarly in implant materials which are used to be implanted in a tissue successfully or for regenerating a tissue or for other purposes. Therefore, even in the case where the use of an organism-derived material is expected to produce desirable results, incompatibility in blood group cannot be avoided and causes the problem of rejection at the time of take or regeneration of the tissue. The term "implant" used herein means an artificial device embedded or transplanted into the body for medical purposes.
Further, the bovine-derived collagen described above has a problem that it is slightly weak in mechanical strength when shaped into a sheet or film and easy to break when used in a narrow width. When this collagen is used in artificial bone or artificial skin, it has a problem of fragility in addition to the above-described problem of biocompatibility.